This is a request for an ADAMHA Research Career Development Award for Paul Worley M.D. Over the past year, there have been several advances in the P.I.'s scientific career which significantly strengthen his candidacy for this award. The focus of the P.I.'s laboratory is to examine cellular mechanisms involved in long-term neuronal responses to synaptic activity. This work is broadly relevant to understanding cortical development as well as aspects of mental health. Genes that are rapidly induced by neuronal activity, and that may be involved in long-term responses, have been cloned from stimulated hippocampus using differential cDNA techniques. Immediate early genes (IEGs) that have been published, or that are currently in review for publication, from our laboratory include a mitogen-inducible cyclooxygenase, termed Cox-2, a novel, inducible member of the Ras family of small GTP-binding proteins, termed Rheb, a zinc-finger transcription factor, termed Egr-3, a member of the TGF beta family of growth factors/signaling molecules, a novel member of the pentraxin family of secreted, calcium-dependent lectins, termed Narp and a novel dendrite and cytoskeleton associated protein, termed Arc. A proposal to study the cellular function of three of these IEGs was recently awarded funding under the RFA "Molecular Mechanisms of Cortical Development" from the NIMH. In addition, the P.I.'s laboratory, in collaboration with Dr. Carol Barnes of the University of Arizona, has made several important observations regarding the physiology of long-term plasticity and the regulation of these genes by synaptic activity in normal and aged rodents. The P.I.'s background includes clinical training in Neurology at Johns Hopkins Hospital and basic science training in the laboratories of Drs. Solomon Snyder and Daniel Nathans. Activities of the P.I. include teaching in the Medical School and the Neuroscience Graduate Program, as well as mentoring three postdoctoral fellows and four Ph.D. students in his laboratory. Plans for career development focus on the cell biological function of the IEGs isolated in his laboratory and their role in long- term neuronal responses to activity and cortical development. The Department of Neuroscience provides an optimal environment for research and scientific development for the P.I.. An RSDA would provide a secure source of salary that is essential for the P.I.'s future career development.